2 OCTOBE R 2018

Scientific Background on the Nobel Prize in Physics 2018

G RO U N D B R E A K I N G I N V E N T I O N S I N L A S E R P H Y S I C S
O P T I C A L T W E E Z E R S A N D G E N E R AT I O N O F H I G H - I N T E N S I T Y,
U LT R A - S H O R T O P T I C A L P U L S E S

The Nobel Committee for Physics

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 Groundbreaking inventions in laser physics
Optical tweezers and generation of high-intensity, ultra-short optical pulses

General introduction
The very first paper describing the principle for an infrared or optical maser arrived to Physical
Review [1] almost exactly 60 years ago (August 26, 1958) and was authored by Arthur L.
Schawlow and Charles H. Townes, then at the Bell Telephone Laboratories in New Jersey. It
represented an extension of the maser technique to the infrared and optical regions. This paper
provided the blueprint for how to construct an optical maser, and it was Theodor H. Maiman [2]
who in 1960 was the first to demonstrate coherent stimulated optical emission. The optical maser
became known to a broader audience interested in popular science when Schawlow published an
article in Scientific American in 1961 [3].

The name “optical maser” was initially used in technical literature, and also in Schawlow’s popular
science article [3]. However, “optical maser” had already been replaced by “laser” (light
amplification by stimulated emission of radiation) when the Royal Swedish Academy of Sciences
awarded the 1964 Nobel Prize in Physics to Townes, Nicolay G. Basov and Aleksandr M.
Prokhorov “for fundamental work in the field of quantum electronics, which has led to the
construction of oscillators and amplifiers based on the laser-maser principle”.

The field of laser physics and its applications grew rapidly after the first discoveries. Laser light
has unique properties such as coherence, directionality, monochromaticity and intensity, which
are very useful properties both in science and in everyday life. Clearly, in the early years of the
laser, the principal driver was the desire to have a device that would generate light waves of the
same purity as radio waves. The first lasers were operated in short bursts, but there was a need
for continuous operation. The development of continuous-wave, frequency-sharp lasers was a
prerequisite for high-resolution laser spectroscopy, which has generated several Nobel Prizes in
Physics.

Another important development in laser physics was the production of short pulses of light,
thanks in particular to the inventions of laser Q-switching [4] and mode locking [5-9], which made
it possible to produce a repetitive train of intense, short laser pulses. Together with the
development of dye lasers [10, 11], this set off a new direction towards shorter and shorter optical
pulses [12-17]. The access to short optical pulses, with durations matching the time-scale for
atomic motion in molecules, led to new research fields in chemistry, and the possibility to study,
in real time, transition states in chemical reactions. These breakthroughs were recognized by the
Nobel Prize in Chemistry in 1999 to Ahmed Zewail.

This year’s Nobel Prize in Physics recognizes two inventions in laser physics that have opened new
frontiers and generated important applications beneficial to the general public. One of them uses
continuous, monochromatic lasers, whereas the other one concerns pulsed lasers.

One half goes to Arthur Ashkin for his invention of the optical tweezers and their application
to biological systems.

The other half goes jointly to Gérard Mourou and Donna Strickland for their method of
generating high-intensity, ultra-short optical pulses.

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Brief history of optical tweezers
Optical tweezers are a laser-based method for trapping and manipulating particles, which takes
advantage of the ability of light to exert force, or radiation pressure. The idea that light could exert
pressure was put forward in 1619 by Johannes Kepler, who postulated that the pressure of light
explains why comet tails always point away from the Sun. In 1873, James Clerk Maxwell showed
theoretically that light can exert pressure, based on his theory of electromagnetism. The existence
of radiation pressure was finally verified experimentally in the early 1900s, by Pyotr Lebedev,
Ernest F. Nichols and Gordon F. Hull. The time it took before its verification is a reminder of how
extraordinarily weak such radiation pressure is under everyday circumstances. With the advent
of lasers in the 1960s, it became possible to study radiation pressure using intense, collimated
beams of light. A pioneer in this field was Arthur Ashkin, whose efforts led to the invention of the
optical tweezers.

An early milestone was Ashkin’s demonstration in 1970 that optical forces, generated by laser
light focused into narrow beams, could displace small dielectric particles in both air and water
[18]. The particles were accelerated in the direction of propagation of the light beam, as intended,
by forward scattering forces. In addition, particles having a refraction index higher than the
surrounding environment were drawn to the centre of the Gaussian beam by a transverse force in
the direction of the intensity gradient, a so-called gradient force. Finally, having made this
observation, Ashkin went on to demonstrate that three-dimensional trapping of particles could
be achieved by using two counter-propagating laser beams [18].

This work was soon followed by Ashkin’s construction of the first single-beam three-dimensional
trap, the optical levitation trap in air [19]. With this method, particles are trapped at a point where
the upward scattering force from a single vertical laser beam is balanced by gravity. However, this
method becomes impractical in situations where the gravitational force is weak and Brownian
motion dominates.

In 1986, Ashkin and coworkers were the first to implement an all-optical single-beam trap [20].
Originally called the single-beam gradient force optical trap, it soon became known as optical
tweezers. This method traps particles by sending a laser beam through an objective lens; this
creates a component of the gradient force that is opposite to the direction of propagation of the
beam (see Figure 1). For trapping to occur, this force component must be sufficiently strong to
balance the forward scattering force, which requires the use of a high numerical aperture, or large
angle of convergence in the beam, provided in practice by a microscope objective lens. It was
demonstrated that this method could trap dielectric particles in water, ranging in size from a few
tens of nanometres up to tens of micrometres [20].

The optical tweezers scheme was originally suggested for the trapping of atoms [22]. Soon after
its first implementation for dielectric particles [20], it was also employed in atom cooling and
trapping experiments [23]. However, Ashkin immediately realised and began to investigate its
potential applicability to biological systems. In groundbreaking studies, he demonstrated that
optical tweezers could trap and manipulate viruses and living cells, switching from a green to an
infrared laser for reduced damage from the intense optical beam [24, 25]. Further applications
included manipulating subcellular components of plant cells [26], and estimating the force
driving organelle transport along microtubules (part of the cytoskeleton) in amoeba cells [27].

Ashkin’s pioneering studies of viruses and living cells were soon followed by new applications of
the optical tweezers method to biological systems by other scientists. An early study by Steven M.
Block, David F. Blair and Howard C. Berg investigated the mechanics of bacterial flagella [28],
which consist of a helical filament connected to a rotary motor that serve to propel the bacterium.
By twisting the bacterium about a tethered flagellum, and calibrating the optical force against
viscous drag, they could measure the torsional compliance of the flagellum.

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Figure 1: Qualitative ray optics description of the restoring backward force in an optical
tweezers trap, for a dielectric sphere that is located below the focus f and assumed to be large
compared with the wavelength of the light. Rays of light carry momentum and are bent by
refraction when passing the dielectric sphere. By conservation of momentum and Newton’s
second law, the momentum change of the refracted rays results in an oppositely directed force
on the sphere. A typical pair of rays, a and b, gives rise to a net force F on the sphere, directed
towards the focus f. In the so-called Rayleigh regime, where the particle is instead small
compared with the wavelength, the optical force can be calculated by treating the particle as a
point dipole. The force obtained can be decomposed into two forces: a scattering force, which is
in the direction of propagation of the beam and is proportional to the intensity, and a gradient
force, which is proportional to the intensity gradient and is directed toward higher intensity.
Source: reference [21].

Molecular-level applications
Optical tweezers are now a widely used tool in biological physics and related areas, and continue
to find new applications. The method is used for non-invasively trapping and manipulating
objects such as single cells and organelles and for performing single-molecule force and motion
measurements. The study of single molecules is made possible by linking them to “handles” that
can be easily trapped with the tweezers, such as micron-sized polystyrene or silica beads. The
beads also act as probes to monitor motion and force.

A basic optical tweezers instrument for trapping micron-sized objects is a relatively simple tool.
However, accurate monitoring of the motion of trapped objects, in aqueous solution at room
temperature, is a challenge that requires advanced instrumentation [29], which may involve the
use of dual traps holding, for instance, the respective ends of a protein or DNA molecule. Progress
in this area has brought single-molecule optical trapping experiments to a level where single base-
pair steps along DNA can be detected [30], corresponding to a spatial resolution at the Ångström
level.

Early subjects for single-molecule studies with optical traps were the physical properties of DNA,
such as relaxation, elasticity and the occurrence of a sharp force-induced transition to an extended
form of DNA [31-33]. Related work was performed using magnetic tweezers [34] and glass micro-
needles [35]. Another optical tweezers–based study demonstrated reversible unfolding of small

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RNA molecules under mechanical force [36]. Force-extension curves for an RNA molecule were
subsequently used for the first experimental test [37] of Jarzynski’s equality in stochastic
thermodynamics, which relates nonequilibrium work distributions to equilibrium free energy
differences [38].

An area in which optical tweezers have proven particularly valuable is the kinetics and mechanics
of molecular motors. These motors convert chemical energy into linear or rotary motion. One
group of molecular motors consists of linear motor proteins that play an essential role in
intracellular transport, muscle contraction and cell division, for example. Basic parameters of a
linear motor include its step size, dwell times and the force generated, which are not directly
accessible with ensemble methods. With optical tweezers, it has been possible to determine
trajectories of single linear motor proteins with sufficient resolution to resolve their stepwise
motion, and thereby obtain information on step size and dwell times, including the role of
fluctuations. A breakthrough was the first direct observation of the stepping motion of kinesin
[39], which transports cellular cargo along microtubules (see Figure 2). A step size of 8 nm was
observed, which corresponds to the length of the repeating unit along microtubules, and the
maximum force produced by kinesin molecules (about 5 pN) could be measured [39]. Related
work analysed the interaction of single myosin molecules with actin filaments [40, 41]. The
myosin-actin interaction generates a relative sliding of myosin and actin filaments for muscle
contraction.

Figure 2: (Left) Sketch of the kinesin-microtubule system studied with optical tweezers in
reference [39]. An optically trapped bead carries a single kinesin molecule that walks along an
immobilized microtubule filament. (Right) Displacement versus time graph for a bead, which
shows that the kinesin molecule executes a walk, pulling the bead forward in a stepwise manner.
Sources: reference [39].

Since these pioneering studies, major advances have been achieved in the precision of optical
trapping experiments, which have enabled studies of an increasingly wide range of molecular
machines. A landmark was the resolution of one-base-pair steps along DNA by the motor RNA
polymerase, which copies DNA into mRNA in the process of transcription [30]. This corresponds
to a step size of 3.4 Å, or about 20 times shorter than that of kinesin mentioned above. The process
of translation, where ribosome machines synthesise proteins based on mRNA transcripts, has also
been studied by optical tweezers experiments, in which the codon-by-codon translation of a single
mRNA molecule by a single ribosome could be followed [42]. Optical tweezers–based
experiments have also provided insight into how proteases use mechanical force to unfold
substrate proteins during targeted protein degradation [43, 44]. These examples illustrate the use
of optical trapping techniques to gain unique insight into the mechanics of fundamental
biomolecular processes.

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Concluding remarks for optical tweezers
The emergence of physical techniques to probe individual molecules, such as single-molecule
fluorescence, single-molecule fluorescence resonance energy transfer, atomic force microscopy,
magnetic tweezers and optical tweezers, has opened up a new window through which we can view
the molecular foundations of biology. Ashkin’s idea of using radiation pressure to trap and
manipulate particles, his invention of the optical tweezers and his pioneering applications of this
method to biological systems were central to this development. His groundbreaking invention was
before its time: its potential would be explored with subsequent improvements to the supporting
technologies for optical tweezers, as well as the development of a surrounding array of methods
that might be used in tandem with them.

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Generation of high-intensity, ultra-short optical pulses
As described in the introduction, the development of optical pulses of short duration was not
followed by a large increase in peak power or energy per pulse. Although the pulses became
shorter, owing in particular to several innovative developments of mode-locked lasers [13-17], the
number of photons in each pulse increased only marginally between 1970 and 1985 (see Figure
3). Nanojoule pulses from a mode-locked oscillator could be amplified to the millijoule level, a
six-order-of-magnitude increase. Larger amplification was hindered by damage to the amplifier
material and optical components of the laser.

Circumventing this problem required increasing the beam diameter, thus decreasing the intensity
experienced by the amplifier medium and preventing damage. This resulted in huge and costly
laser installations that could only be realised by national research institutes. Moreover, these large
lasers operated at low repetition rates, as little as a few shots per day, in order to give the
amplifiers sufficient time to cool between shots.

Figure 3. The history of pulsed laser technology in terms of peak intensity. After an initial
increase in intensity during the 1960s, as described in the text, only an incremental increase
occurred during more than a decade. The invention of the CPA technique for optical pulses by
Strickland and Mourou in 1985 [45] dramatically changed the situation. The values on the y-
axis are indicative because the intensity depends on how sharply the laser beam is focused.

The breakthrough came in 1985, when Donna Strickland and Gérard Mourou invented the
chirped pulse amplification (CPA) technique for optical pulses [45]. The inspiration came from
radar technology, just as Townes had benefitted from his experience in radar systems when
inventing the maser, as well as in research related to optical communication [46, 47].

The CPA technique proceeds in three steps: 1) an ultra-short laser pulse is stretched in time by
several orders of magnitude, so that its peak power is correspondingly reduced, 2) it is amplified
in a laser material without damaging it, 3) it is compressed in time back to its original duration,
resulting in very high peak power. In the original implementation of Strickland and Mourou [45],

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in the first step, a short, low-energy, nanojoule pulse from a mode-locked Nd:YAG laser was
coupled into a single-mode optical fibre and stretched to a duration of about 300 ps. The pulse
was linearly chirped (see Figure 4) in the fibre by group velocity dispersion and self-phase
modulation (a nonlinear optical effect inducing a varying refractive index) [48]. The dispersion in
the fibre was positive, so that the low-frequency (red) part of the pulse propagated faster than the
high-frequency (blue) part. In the second step (see Figure 5), Strickland and Mourou then
amplified the chirped pulse in a Nd:glass regenerative amplifier. In the final step, the long chirped
pulse was compressed by a double grating compressor [49] to 2 ps; the energy of the amplified
pulse was 1 mJ.

The CPA concept and further progress beyond the original demonstration were presented at the
Conference on Lasers and Electro-Optics in San Francisco, June 9-13, 1986 [50] and at the Fifth
OSA Topical Meeting, Snowmass, Colorado, June 16-19, 1986 [51]. Shortly after the breakthrough
paper [45], CPA-based lasers with peak powers exceeding 1 TW were constructed [50−53].

Figure 4. Chirped optical pulse, with the electric field plotted against time. The chirp of the
pulse is the time dependence of its instantaneous frequency. The pulse is up-chirped, which
means that the frequency increases with time. (Reproduced from http://rp-
photonics.com/chirp.html.)

The first improvement of the CPA-technique occurred very soon after the breakthrough paper,
when the fibre used to stretch the pulse was replaced by a pair of diffraction gratings [54-56].
Amplification of pulses from nanojoule to joule level was demonstrated [53], i.e. a nine-orders-
of-magnitude increase in energy per pulse. A standard CPA configuration is shown in Figure 5.
The invention of the CPA technique enabled a giant leap in the intensity of optical pulses; see
Figure 3.

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Figure 5. The standard CPA configuration. The chirp is illustrated with colours. Initially the
gain medium (amplifier) was Nd:glass, whereas today, another common gain medium is
Ti:sapphire. (Reproduced from Center for Ultrafast Optical Science, University of Michigan in
Ann Arbor.)

Several new areas of research and practical applications followed the invention of CPA. CPA
technology and important offspring, such as the Optical Parametric CPA [57], were used in the
push for higher intensities (see Figure 3). Soon after the invention of CPA [45], the acronym T3
emerged, to describe a tabletop terawatt laser. Typical parameters for the first Nd:glass systems
were 1 J/pulse and a pulse duration of about 1 ps. Shorter pulses, below 100 fs, were obtained
using Ti:sapphire [58]. Soon the vision of a petawatt laser system emerged [52], which took a
decade to be realised at the Lawrence Livermore National Laboratory in 1999 [59].

Figure 3 (displaying focused intensity) shows that peak power or intensity have continued to grow
at a rapid pace over many years. The development is also strikingly illustrated by two reviews
separated by nearly two decades [60, 61]. While the first review was written at about the time the
first petawatt laser was constructed [59], the latter review described no fewer than 50 petawatt-
class lasers worldwide, either currently operational, under construction or in the planning phase
[61].

One petawatt is no longer an upper limit. Many projects now aim for higher power and intensity
and are in various stages of development. For example, the Extreme Light Infrastructure (ELI)
Beamlines facility in Prague, Czech Republic, will include a 10-PW laser system. Focused intensity
levels exceeding 1023 W/cm2 are anticipated, opening new fields of research. High-field physics
could open windows to new extreme states of matter such as radiation-dominated ones, high-
pressure quantum ones, warm dense matter (WDM) and ultra-relativistic plasmas. High-energy-
density physics (HEDP) is of fundamental importance for research in the field of laboratory
astrophysics and inertial confinement fusion.

A second aspect of equal importance to the frontier of high-intensity physics was that CPA
technology led to laser systems with high peak power due to short pulse duration, but modest
pulse energy, thus enabling high repetition rates. Affordable tabletop lasers (T3) that fit university
groups’ budgets could deliver pulses at a rate of 10 Hz with peak power equal to that of the few
shots per day delivered by the very large and expensive lasers used in inertial confinement
experiments for nuclear fusion. These tabletop systems opened new research areas such as strong-
field physics, attosecond science, and laser-plasma acceleration, described below.

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Applications
A third and very practical aspect of CPA technology was the fact that it became possible to
construct compact and user-friendly, high-power, ultra-short laser systems suitable for industrial
and medical applications, in addition to basic physics research. The CPA technology opened up a
wide range of research areas due to the widespread availability of high-power, ultra-short pulse
lasers with high repetition rates.

Strong-field physics and attosecond science

Atoms and molecules exposed to low-intensity light do not change their properties as a
consequence of the interaction. If the light is tuned to be in resonance with a transition, an
excitation can occur, and if the photon energy is sufficiently high, an electron may be liberated in
the process of ionization. An interesting regime occurs when the light field strength becomes
comparable to that needed to bind electrons in atoms or molecules. This is called the strong-field
regime of atomic physics [62-70].

Several interesting physical phenomena follow the ionization process in a strong laser field. The
atom can be ionized by absorbing many more photons than required, leading to the ejection of
electrons with very high kinetic energy, a process called above-threshold ionization (ATI) [69, 70].
High Harmonic Generation (HHG) of the laser light [66, 67] was initially discovered without CPA
technology, but the widespread exploration of strong-field physics that followed was a direct
consequence of CPA. Detailed experimental studies of HHG using CPA-based femtosecond lasers
led to the elaboration of an intuitive semi-classical interpretation of the physics in strong laser
fields [70-72], presented in Figure 6.

Figure 6. Illustration of the three-step recollision model of HHG. In the first step, the laser field
causes tunnelling ionization; in the second step, the laser field first accelerates the electron.
When the field reverses in the next half-cycle, the free electron may return back to the ion and
recombine. In this third step, an extreme ultraviolet photon is emitted. (Reproduced from J.P.
Marangos and M. Oppermann, Attosecond generation and high field physics, in Ultrafast Non-
Linear Optics (Scottish Graduate Series), R. Thomson, ed., Springer, New York, p. 45 (2013).)

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However beautiful, the femtosecond laser technology developed during the 1960s, 1970s and
1980s was unable to break the 1-fs-pulse–duration limit. Shortly after the first experimental
realisations of high harmonics, it was suggested that, in analogy with mode locking, high-order
harmonics could lead to pulses shorter than 1 fs [73]. A decade later, after building on many
improvements and insights into HHG by means of CPA-based lasers, the first attosecond pulses
were experimentally observed [74, 75]. This was the birth of a new research field − attosecond
science. For the first time, the electron dynamics inside atoms, molecules and matter in the
condensed phase could be probed [76].

Laser-plasma acceleration

Accelerator technology is still totally dominated by radiofrequency (RF) accelerators operating in

a frequency range from 100 MHz up to several gigahertz. This technology is mature, robust and
serves the operating requirements for many accelerators. However, it has some disadvantages. If
the goal is construction of an accelerator at the high-energy frontier, the limited acceleration
gradient requires the accelerator to be very large and hence very expensive. When high-energy
particles (most often protons) are needed for radiation therapy of tumours, for example, a heavy
and bulky RF accelerator is difficult to fit into a hospital environment.

Researchers suggested in 1979 that an intense laser could generate a plasma wave (the wakefield)
that could accelerate electrons to 1 GeV over a distance of 1 cm [77]. The key to this very high
acceleration gradient is having a high-power laser. Figure 7 illustrates the principle for laser-
plasma acceleration.

Figure 7. Schematic illustration of laser-plasma acceleration. An intense laser pulse drives a

plasma wave (wake) in a plasma channel, which also guides the laser pulse and prevents
diffraction. Plasma background electrons injected with the proper phase can be accelerated and
focused by the wake. (Reproduced from W.P. Leemans (2010), White Paper of the ICFA-ICUIL
Joint Task Force – High Power Laser Technology for Accelerators, http://icfa-
bd.kek.jp/WhitePaper_final.pdf.)

At Lawrence Berkeley National Laboratory in California, a petawatt-class laser at the Berkeley

Lab Laser Accelerator (BELLA) facility is used to accelerate electrons to 4.2 GeV over a distance
of 9 cm [78]. This is an acceleration gradient of at least two orders of magnitude higher than what
can be obtained with RF technology. That there are many remaining challenges before laser
accelerators can be used for medical applications is well understood [79].

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High-intensity lasers in industry and medicine

High-intensity, ultra-short laser pulses are very powerful when high precision is needed because
of the minimal thermal energy deposition in materials, resulting in negligible collateral damage
beyond the desired interaction volume. The CPA technology has made it possible to build compact
and user-friendly laser systems suitable for industrial and medical applications. The intensity
level can be adjusted to be optimal for different applications: for example, lower levels for heat
treating and higher for material removal. High-aspect-ratio holes that are required for stents can
be drilled with femtosecond lasers.

In recent years, femtosecond lasers have become available for clinical use in refractive surgical
procedures to treat myopia and astigmatism worldwide. In LASIK (laser-assisted in situ
keratomileusis; see Figure 8), a femtosecond laser offers high precision for making the corneal
flap, which is required for the excimer laser to have access to and reshape the corneal stroma.
With the introduction of an all-in-one femtosecond laser procedure [80], which does not require
the creation of a flap, a very small incision of about 4 mm or less is created in order to remove the
photo-ablated refractive lenticule. Removing the lenticule changes the shape of the cornea, so that
the desired refractive correction is obtained. Typical femtosecond pulse energies are 120 nJ [81].

Figure 8. Schematic illustration of an all-in-one femtosecond laser refractive surgical

procedure. The green dotted lines represent the beams from a CPA-based femtosecond laser
operating at fairly low pulse energies of 120 nJ/pulse, but at a high repetition rate of more than
100 kHz. The laser beam is continuously moved in circles with decreasing radii, as in a spiral
moving inwards. The femtosecond laser creates a small lens-shaped bit of tissue to be removed,
a lenticule, within the cornea. The laser is also used to create a small incision in the cornea
through which the lenticule is mechanically removed. The laser is focused to a few micrometres,
so that the laser ablation process creating the lenticule can be positioned with high precision.
The lenticule is typically 6 mm in diameter and 100 µm in thickness in the centre. By removing
the lenticule, the focal length is prolonged, so that focus is moved to the retina and myopia
corrected.

Concluding remarks for generation of high-intensity, ultra-short optical

pulses
The invention by Mourou and Strickland of the CPA technique has opened many avenues for
researchers both in basic and applied science, resulting in beneficial applications. Expanding the
frontiers of CPA is an ongoing endeavour.

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References

[1] A.L. Schawlow and C.H. Townes, Infrared and optical masers, Phys. Rev. 112, 1940 (1958)

[2] T.H. Maiman, Stimulated optical radiation in ruby, Nature 187, 493 (1960)

[3] A.L. Schawlow, Optical masers, Scientific American 204 (6), 52 (1961)

[4] F.J. McClung and R.W. Hellwarth, Giant optical pulsations from ruby, J. Appl. Phys. 33, 828
(1962)

[5] L.E. Hargrove, R.L. Fork and M.A. Pollack, Locking of He−Ne laser modes induced by
synchronous intracavity modulation, Appl. Phys. Lett. 5, 4 (1964)

[6] M. DiDomenico Jr., Small-signal analysis of internal (coupling-type) modulation of lasers,

J. Appl. Phys. 35, 2870 (1964)

[7] A. Yariv, Internal modulation in multimode laser oscillators, J. Appl. Phys. 36, 388 (1965)

[8] H.W. Mocker and R.J. Collins, Mode competition and self-locking effects in a Q-switched
ruby laser, Appl. Phys. Lett. 7, 270 (1965)

[9] A.J. DeMaria, D.A. Stetser and H. Heynau, Self mode-locking of lasers with saturable
absorbers, Appl. Phys. Lett. 8, 174 (1966)

[10] P.P. Sorokin and J.R. Lankard, Stimulated emission observed from an organic dye, chloro-
aluminum phthalocyanine, IBM J. Res. Dev. 10, 162 (1966)

[12] F.P. Schäfer, W. Schmidt and J. Volze, Organic dye solution laser, Appl. Phys. Lett. 9, 306
(1966)

[13] E.P. Ippen, C.V. Shank and A. Dienes, Passive mode locking of the the cw dye laser, Appl.
Phys. Lett. 21, 348 (1972)

[14] C.V. Shank and E.P. Ippen, Subpicosecond kilowatt pulses from a mode-locked cw dye laser,
Appl. Phys. Lett. 24, 373 (1974)

[15] I.S. Ruddock and D.J. Bradley, Bandwidth-limited subpicosecond pulse generation in mode-
locked cw dye lasers, Appl. Phys. Lett. 29, 296 (1976)

[16] R.L. Fork, B.I. Greene and C.V. Shank, Generation of optical pulses shorter than 0.1 psec by
colliding pulse mode locking, Appl. Phys. Lett. 38, 671 (1981)

[17] W.J. Tomlinson, R.H. Stolen and C.V. Shank, Compression of optical pulses chirped by self-
phase modulation in fibers, J. Opt. Soc. Am. B 1, 139 (1984)

[18] A. Ashkin, Acceleration and trapping of particles by radiation pressure, Phys. Rev. Lett. 24,
156 (1970)

[19] A. Ashkin and J.M. Dziedzic, Optical levitation by radiation pressure, Appl. Phys. Lett. 19,
283 (1971)

[20] A. Ashkin, J.M. Dziedzic, J.E. Bjorkholm and S. Chu, Observation of a single-beam gradient
force optical trap for dielectric particles, Opt. Lett. 11, 288 (1986)

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[21] A. Ashkin, Force of a single-beam gradient laser trap on a dielectric sphere in the ray optics
regime, Biophys. J. 61, 569 (1992)

[22] A. Ashkin, Trapping of atoms by resonance radiation pressure, Phys. Rev. Lett. 40, 729
(1978)

[23] S. Chu, J.E. Bjorkholm, A. Ashkin and A. Cable, Experimental observation of optically
trapped atoms, Phys. Rev. Lett. 57, 314 (1986)

[24] A. Ashkin and J.M. Dziedzic, Optical trapping and manipulation of viruses and bacteria,
Science 235, 1517 (1987)

[25] A. Ashkin, J.M. Dziedzic and T. Yamane, Optical trapping and manipulation of single cells
using infrared laser beams, Nature 330, 769 (1987)

[26] A. Ashkin and J.M. Dziedzic, Internal cell manipulation using infrared laser traps, Proc.
Natl. Acad. Sci. USA 86, 7914 (1989)

[27] A. Ashkin, K. Schütze, J.M. Dziedzic, U. Euteneuer and M. Schliwa, Force generation of
organelle transport measured in vivo by an infrared laser trap, Nature 348, 346 (1990)

[28] S.M. Block, D.F. Blair and H.C. Berg, Compliance of bacterial flagella measured with optical
tweezers, Nature 338, 514 (1989)

[29] T.T. Perkins, Ångström-precision optical traps and applications, Annu. Rev. Biophys. 43,
279 (2014)

[30] E.A. Abbondanzieri, W.J. Greenleaf, J.W. Shaevitz, R. Landick and S.M. Block, Direct
observation of base-pair stepping by RNA polymerase, Nature 438, 460 (2005)

[31] T.T. Perkins, S.R. Quake, D.E. Smith and S. Chu, Relaxation of a single DNA molecule
observed by optical microscopy, Science 264, 822 (1994)

[32] S.B. Smith, Y. Cui and C. Bustamante, Overstretching B-DNA: the elastic response of
individual double-stranded and single-stranded DNA molecules, Science 271, 795 (1996)

[33] M.D. Wang, H. Yin, R. Landick, J. Gelles and S.M. Block, Stretching DNA with optical
tweezers, Biophys. J. 72, 1335 (1997)

[34] S.B. Smith, L. Finzi and C. Bustamante, Direct mechanical measurements of the elasticity of
single DNA molecules by using magnetic beads, Science 258, 1122 (1992)

[35] P. Cluzel, A. Lebrun, C. Heller, R. Lavery, J.L. Viovy, D. Chatenay and F. Caron, DNA: an
extensible molecule, Science 271, 792 (1996)

[36] J. Liphardt, B. Onoa, S.B. Smith, I. Tinoco Jr. and C. Bustamante, Reversible unfolding of
single RNA molecules by mechanical force, Science 292, 733 (2001)

[37] J. Liphardt, S. Dumont, S.B. Smith, I. Tinoco Jr. and C. Bustamante, Equilibrium
information from nonequilibrium measurements in an experimental test of Jarzynski’s equality,
Science 296, 1832 (2002)

[38] C. Jarzynski, Nonequilibrium equality for free energy differences, Phys. Rev. Lett. 78, 2690
(1997)

13 (16)
[39] K. Svoboda, C.F. Schmidt, B.J. Schnapp and S.M. Block, Direct observation of kinesin
stepping by optical trapping interferometry, Nature 365, 721 (1993)

[40] J.T. Finer, R.M. Simmons and J.A. Spudich, Single myosin molecule mechanics: piconewton
forces and nanometre steps, Nature 368, 113 (1994)

[41] J.E. Molloy, J.E. Burns, J. Kendrick-Jones, R.T. Tregear and D.C.S. White, Movement and
force produced by a single myosin head, Nature 378, 209 (1995)

[42] J.D. Wen, L. Lancaster, C. Hodges, A.C. Zeri, S.H. Yoshimura, H.F. Noller, C. Bustamante
and I. Tinoco Jr, Following translation by single ribosomes one codon at a time, Nature 452,
598 (2008)

[43] M.E. Aubin-Tam, A.O. Olivares, R.T. Sauer, T.A. Baker and M.J. Lang, Single-molecule
protein unfolding and translocation by an ATP-fueled proteolytic machine, Cell 145, 257 (2011)

[44] R.A. Maillard, G. Chistol, M. Sen, M. Righini, J. Tan, C.M. Kaiser, C. Hodges, A. Martin and
C. Bustamante, ClpX(P) generates mechanical force to unfold and translocate its protein
substrates, Cell 145, 459 (2011)

[45] D. Strickland and G. Mourou, Compression of amplified chirped optical pulses, Opt.
Commun. 56, 219 (1985)

[46] J. Desbois, F. Gires and P Turnois, A new approach to picosecond laser pulse analysis
shaping and coding, IEEE J. Quant. Electron. QE-9, 213 (1973)

[47] R.L. Fork, O.E. Martinez and J.P. Gordon, Negative dispersion using pairs of prismas, Opt.
Lett. 9, 150 (1984)

[48] B. Nikolaus and D. Grischkowsky, 12x pulse compression using optical fibers, Appl. Phys.
Lett. 42, 1 (1983)

[49] E. Treacy, Optical pulse compression with diffraction gratings, IEEE J. Quant. Electr. QE-
5, 454 (1969)

[50] D. Strickland, P. Maine, M. Bouvier, S. Williamson and G. Mourou, Picosecond pulse

amplification using pulse compression techniques, in Conference on Lasers and Electro-Optics,
G. Bjorklund, E. Hinkley, P. Moulton and D. Pinnow, eds., OSA Technical Digest (Optical Society
of America, 1986), paper THL1

[51] D. Strickland, P. Maine, M. Bouvier, S. Williamson and G. Mourou, Picosecond pulse

amplification using pulse compression techniques, in Ultrafast phenomena V: Proceedings of
the Fifth OSA Topical Meeting, Snowmass, Colorado, June 16-19, 1986. G.R. Fleming and A.E.
Siegman, eds., (Berlin, Heidelberg, New York, Springer Verlag, 1986), p. 38

[52] P. Maine, D. Strickland, P. Bado, M. Pessot and G. Mourou, En route vers le Petawatt, Rev.
Phys. Appl. (Paris) 22, 1657 (1987)

[53] P. Maine, D. Strickland, P. Bado, M. Pessot and G. Mourou, Generation of ultrahigh peak
power pulses by chirped pulse amplification, IEEE J. Quantum Electron. QE-24, 398 (1988)

[54] O.E. Martinez, Grating and prism compressors in the case of finite beam size, J. Opt. Soc.
Am. B 3, 929 (1986)

14 (16)
[55] O.E. Martinez, 3000 times grating compressor with positive group velocity dispersion:
Application to fiber compensation in the 1.3-1.6 µm region, IEEE J. Quant. Electron. QE-23, 59
(1987)

[56] M. Pessot, P. Maine and G. Mourou, 1000 times expansion/compression of optical pulses
for chirped pulse amplification, Opt. Commun. 62, 419 (1987)

[57] A. Dubietis, G. Jonusauskas and A. Piskarskas, Powerful femtosecond pulse generation by

chirped and stretched pulse parametric amplification in BBO crystal, Opt. Commun. 88, 437
(1992)

[58] P. Moulton, Ti-doped sapphire: tunable solid-state laser, Opt. News 8, 9 (1982)

[59] M.D. Perry, D. Pennington, B.C. Stuart, G. Tietbohl, J.A. Britten, C. Brown, S. Herman, B.
Golick, M. Kartz, J. Miller, H.T. Powell, M. Vergino and V. Yanovsky, Petawatt laser pulses, Opt.
Lett. 24, 160 (1999)

[60] S. Backus, C.G. Durfee III, M.M. Murnane and H.C. Kapteyn, High power ultrafast lasers,
Rev. Sci. Instrum. 69, 1207 (1998)

[61] C. Danson, D. Hiller, N. Hopps and D. Neely, Petawatt class lasers worldwide, High Power
Laser Science and Engineering, vol. 3, p. 1 (2015)

[62] L.V. Keldysh, Ionization in the field of a strong electromagnetic wave, Sov. Phys. JETP 20,
1307 (1965)

[63] F.H.M. Faisal, Multiple absorption of laser photons by atoms, J. Phys. B 6, L89 (1973)

[64] H.R. Reiss, Effect of an intense electromagnetic field on a weakly bound system, Phys. Rev.
22, 1786 (1980)

[65] M.V. Ammosov, N.B. Delone and V.P. Krainov, Tunnel ionization of complex atoms and
atomic ions in an alternating electric field, Sov. Phys. JETP 64, 1191 (1986)

[66] M. Ferray, A. L’Huillier, X.F. Li, L.A. Lompre, G. Mainfray and C. Manus, Multiple-harmonic
conversion of 1064 nm radiation in rare gases, J. Phys. B 21, L31 (1988)

[67] X.F. Li, A. L’Huillier, M. Ferray, L.A. Lompré and G. Mainfray, Multiple-harmonic
generation in rare gases at high laser intensity, Phys. Rev. A 39, 5751 (1989)

[68] S. Augst, D. Strickland, D.D. Meyershofer, S.L. Chin and J.H. Eberly, Tunneling ionization
of noble gases in a high-intensity laser field, Phys. Rev. Lett. 63, 2212 (1989)

[69] P. Agostini, F. Fabre, G. Mainfray, G. Petite and N.K. Rahman, Free-free transitions
following six-photon ionization of xenon atoms, Phys. Rev. Lett. 42, 1127 (1979)

[70] K.J. Schafer, B. Yang, L.F. DiMauro and K.C. Kulander, Above threshold ionization beyond
the high harmonic cutoff, Phys. Rev. Lett. 70, 1599 (1993)

[71] K.C. Kulander, K.J. Schafer and J.L. Krause, Dynamics of short-pulse excitation, ionization
and harmonic conversion, in Super-Intense Laser-Atom Physics, NATO ASI Series (Series B:
Physics), 316, 95 (1993)

[72] P.B. Corkum, Plasma perspective on strongfield multiphoton ionization, Phys. Rev. Lett.
71, 1994 (1993).

15 (16)
[73] Gy. Farkas and Cs. Tóth, Proposal for attosecond light pulse generation using laser induced
multiple-harmonic conversion processes in rare gases, Phys. Lett. A 168, 447 (1992)

[74] P.M. Paul, E.S. Toma, P. Breger, G. Mullot, F. Augé, Ph. Balcou, H.G. Muller and P. Agostini,
Observation of a train of attosecond pulses from high harmonic generation, Science 292, 1689
(2001)

[75] M. Hentschel, R. Kienberger, C. Spielmann, G.A. Reider, N. Milosevic, T. Brabec, P. Corkum,

U. Heinzmann, M. Drescher and F. Krausz, Attosecond metrology, Nature 414, 509 (2001)

[76] F. Calegari, G. Sansone, S. Stagira, C. Vozzi and M. Nisoli, Advances in attosecond science,
J. Phys. B 49, 062001 (2016)

[77] T. Tajima and J.M. Dawson, Laser electron accelerator, Phys. Rev. Lett. 43, 267 (1979)

[78] W.P. Leemans, A.J. Gonsalves, H.-S. Mao, K. Nakamura, C. Benedetti, C.B. Schroeder, Cs.
Tóth, J. Daniels, D.E. Mittelberger, S.S. Bulanov, J.-L. Vay, C.G.R. Geddes and E. Esarey, Multi-
GeV electron beams from capillary-discharge-guided subpetawatt laser pulses in the self-
trapping regime, Phys. Rev. Lett. 113, 245002 (2014).

[79] U. Linz and J. Alonso, What will it take for laser driven proton accelerators to be applied to
tumor therapy?, Phys. Rev. ST Accel. Beams 10, 094801 (2007)

[80] W. Sekundo, K.S. Kunert and M Blum, Small incision corneal refractive surgery using the
small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic
astigmatism: results of 6 month prospective study, Br. J. Ophthalmol. 95, 335 (2011)

[81] F. Lin, Y. Xu and Y. Yang, Comparison of the visual results after SMILE and femtosecond
laser-assisted LASIK for myopia, J. Refract. Surg. 30, 248 (2014)

16 (16)